Chronic Rhinosinusitis (CRS) is a persistent symptomatic inflammation of the nasal and paranasal sinuses characterized by at least 8-12 weeks of two or more symptoms selected from nasal congestion or blockage, anterior or posterior nasal discharge, facial pressure or pain, and reduction or loss of smell. CRS is further categorized based on the presence or absence of nasal polyps (CRS without nasal polyps, CRSsNP; or CRS with nasal polyps, CRSwNP). CRSsNP is frequently associated with facial pressure or pain, whereas CRSwNP is frequently associated with a reduced ability to smell and detect odors (hyposmia). (Bachert et al. (2014) World Allergy Organ J 7(1):25; European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2012).)
CRS is considered a public health problem having a significant social and economic impact. CRS has been variously estimated to affect from 5% to 15% of the general population, and overall annual economic burden of CRS in the United States alone has been estimated to be $22 billion in 2014. (Bachert et al., supra; Smith et al. (2015) Laryngoscope doi: 10.1002/lary.25180.) Although not considered a life-threatening disease, the measurable impact of CRS on quality of life is profoundly negative, including increased sleep dysfunction, anxiety and depression in patients having CRS. (See, e.g., Alt et al. (2013) Int Forum Allergy Rhinol 3(11):941-949; Katotomichelakis et al. (2014) Int J Psychiatry Med 48(2):83-94.)
While the exact etiology of CRS has not been clearly defined, a number of hypotheses have been considered. The mucosa lining the nasal and paranasal cavities is the interface with inhaled irritants, aero-allergens, commensal organisms, and pathogens. Because of the importance of the epithelium as a mediator of immune defense, it has been suggested that defects in a broad set of epithelium-related genes could contribute to a dysfunctional immune response to environmental agents in patients with CRS. (Kern et al. (2008) Am J Rhinol 22(6):549-559.) Diminished host defense may contribute to local microbial proliferation fostering the development of CRS. While the role of microbes as causative agents in CRS is not clear, bacterial and/or fungal infection and biofilms may contribute to the propagation of CRS. (Cain and Lal (2013) Infect Drug Resist 6:1-14.) Endoscopic surgery is the only known treatment option for effective removal of obstructive nasal polyps from CRSwNP patients; however, estimated polyp recurrence rates are unacceptably high even with use of chronic corticosteroid therapy. (Wynn and Har-El (2004) Laryngoscope 114(5):811-813; Newton and Ah-See (2008) Ther Clin Risk Manag 4(2):507-512.) Effective preventative therapy against polyposis in CRS disease, before and after surgical intervention, clearly remains an important unmet medical need.
Despite many decades of world-wide effort toward discovery of therapeutic approaches against CRS, effective treatment options for this disease remain limited in scope and largely inadequate. While both CRSwNP and CRSsNP are typically treated with intranasal corticosteroids (INS), second line antibiotics are often recommended in CRSsNP but are only recommended in CRSwNP when symptoms indicate infection (pain or purulence). Saline irrigation and oral steroids may also be recommended when appropriate. (Kaplan (2013) Can Fam Physician 59(12):1275-1281.) Within the past two decades, however, and particularly since the advent of the NIH Human Microbiome Project in 2008, a large body of compelling research has linked inappropriate microbial colonization of the paranasal mucosa and a consequent state of chronic immuno-inflammatory activation to the distinctive pathophysiology of CRS. (Chalermwatanachai et al. (2015) World Allergy Organ J 8(1):3; Hamilos (2014) J Allergy Clin Immunol 33(3):640-653.) While various symptoms of CRS have all been reported to respond favorably to chronic INS therapy, it is clear that INS therapy can do little to resolve the underlying cause of microbial-related CRS disease.
To date, no effective means of restoring host-microbial balance and mitigating disease in patients with CRS has been found. A large number of systemic and topical bactericidal or fungicidal drugs have been explored in the context of CRS disease, often showing very good short-term efficacy for reduction of microbial density in the paranasal mucosa and concomitant alleviation of CRS clinical symptoms. (See, e.g., Kaplan, supra; Lim et al. (2008) Am J Rhinol 22(4):381-389; Huang and Govindaraj (2013) Curr Opin Otolaryngol Head Neck Surg 21(1):31-38.) Long-term use of antibiotics is not recommended, however, due to concerns over the danger of promoting expansion of resistant bacteria. (Kennedy and Borish (2013) Am J Rhinol Allergy 27(6):467-472.) Alternatively, clinical use of various probiotic agents and other “microbiome rebalancing” strategies has been suggested for CRS disease. (Cleland et al. (2014) Int Forum Allergy Rhinol 4(4):309-314; Mukerji et al. (2009) Otolaryngol Head Neck Surg 140(2):202-208.)
A number of alternative therapies have been postulated for CRS disease including intranasal irrigations with colloidal silver, surfactant solutions derived from commercial baby soap products, sodium hyaluronate, methylglyoxal, xylitol solution, and isotonic or hypertonic saline. (Goggin et al. (2014) Int Forum Allergy Rhinol 4(3):171-175; Chiu et al. (2008) Am J Rhinol 22(1):34-37; Casale et al. (2014) Am J Rhinol Allergy 28(4):345-348; Kilty et al. (2011) Int Forum Allergy Rhinol 1(5):348-350; Weissman et al. (2011) Laryngoscope 121(11):2468-72; van den Berg et al. (2014) Otolaryngol Head Neck Surg 150(1):16-21; Ural et al. (2009) J Laryngol Otol 123(5):517-21.) Ultrasound treatment to disrupt bacterial biofilm in CRS has also been suggested. (Ansari et al. (2012) Physiother Theory Pract 28(2):85-94; Young et al. (2010) J Laryngol Otol 124(5):495-499.)
There remains a need in the art for an effective treatment of chronic rhinosinusitis. The present invention provides an efficacious treatment to reduce the symptoms of chronic rhinosinusitis and improve the quality of life of those suffering from CRS. The invention also provides for the use of a boric acid formulation for the treatment of chronic rhinosinusitis in a patient in need.